Formation of specific protein-DNA complexes is manifested by a significant negative heat capacity change. This has been considered as evidence for hydrophobic forces playing dominant role in complex formation. However, in many cases the interaction results in structural changes in both, protein and DNA. It remains unclear and debatable to what extent the observed changes in heat capacity should be attributed simply to association of free components or to structural changes that accompany binding. Two experimental systems are considered: the sequence-specific complexes of the mouse HMG box Sox-5 with DNA targets of different length and of the 62 AA long fragment of the yeast transcriptional factor GCN4 with the closely related AP1 and ATF/CREB sites. In both cases the DNA-binding domain of the protein is largely disordered in isolation and, therefore, binding to DNA necessarily involves simultaneous refolding. On the other hand, the DNA duplex also undergoes unwinding and bending upon complex formation. The determination of the energetic parameters that characterize the thermodynamic coupling between association and structural rearrangements of components will be accomplished by combination of ITC and DSC.